By the time diseases of the retina are detected, serious damage has often already been done. An advanced optical imaging instrument utilizing adaptive optics can be used to directly visualize the cellular structure of the retina in the living human eye. Adaptive optics is a technology for measuring and correcting the optical imperfections in the human eye. When adaptive optics is combined with an imaging platform, highly detailed images of the human retina can be acquired. Our research utilizes this technology to image cells in patients eyes through the Adaptive Optics Clinic within the NIH Clinical Center. Processing of adaptive optics is highly time-consuming and labor intensive. Currently, there are very few publicly-available tools for handling of adaptive optics data. We have been actively developing novel computational tools for the computer aided analysis of adaptive optics imaging data which will greatly enhance and accelerate our progress towards assembling a normal database of adaptive optics imaging data. Examples of such tools that we have developed include the automated identification, segmentation, and tracking of photoreceptors and RPE cells. We have started to make these software tools publicly-available through the NEI Commons which currently includes portals to two open-source software packages: Cone Detection and Cone Segmentation. We are actively developing and implementing new technologies for improving our state-of-the-art, custom-built adaptive optics instrument in the NEI eye clinic with the overarching goal of augmenting the translational research capabilities at the NIH Clinical Center. We have carried out extensive experiments characterizing the time course of intravenously-delivered indocyanine green (ICG) dye uptake into the RPE using adaptive optics enhanced indocyanine green (AO-ICG) imaging which we pioneered for the first time at the NIH Clinical Center. On the instrumentation front, we are continuing to collaborate with Dr. Zhang at UCLA to develop and apply high speed adaptive optics imaging approaches for vascular imaging. We are continuing to collaborate with Drs. Hammer and Liu at the FDA to fine tune adaptive optics optical coherence tomography technologies. Electronics and real-time programming enhancements are under development through collaboration with Drs. Pursley and Pohida, CIT. Progress towards these projects is facilitated by ongoing collaborations with NIH and NEI IT. Finally, through collaboration with Drs. Huryn, Zein, Brooks, Wong, Chew, Cukras, Wiley, Keenan, Hufnagel, and Jeffrey, we are currently exploring how sight-threatening diseases affect retinal cells. These experiments span basic science, translational research, and clinical imaging and involve collaborations with Drs. Fariss, Smelkinson, Schwartz, and Bharti. Translation of our technology and tools into these patients will lead to the ability to monitor the progression of disease in actual patients at the cell-to-cell level.